crossing96/oncoscreening huggingface dataset:
microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis.	BACKGROUND: The downregulation of microRNA (miR)-451a has been reported in bladder cancer (BCa) tissues. Herein, we elucidated the role of miR-451a in BCa with the involvement of DNA methyltransferase 3B (DNMT3B). METHODS: We first screened the differentially expressed miRNAs from the serum of 12 BCa patients and 10 healthy controls in the BCa database GSE113486. Subsequently, we detected miR-451a expression and CpG island methylation of the promoter in BCa cells T24 and 5637 with DNMT3B knockdown. The downstream mRNAs of miR-451a were predicted by bioinformatics and KEGG enrichment analysis. Afterwards, the expression patterns of DNMT3B, miR-451a and erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EPHA2) were altered in BCa cells to test the ability of cell proliferation, apoptosis, migration as well as invasion. Finally, the effect of miR-451a and DNMT3B was evaluated in vivo. RESULTS: miR-451a was significantly reduced in serum of BCa patients and cell lines. Moreover, the expression of DNMT3B in BCa cells was significantly increased, thus promoting methylation of the miR-451a promoter, resulting in miR-451a inhibition. Additionally, we found that miR-451a targeted and negatively regulated EPHA2, while EPHA2 could activate the PI3K/AKT signaling, driving BCa cell growth and metastasis. CONCLUSIONS: Our study proposed and demonstrated that miR-451a downregulation mediated by DNMT3B is critical for proliferation, migration, and invasion of BCa, which may be beneficial for developing more effective therapies against BCa.	bladder
Prognostic value of pretreatment inflammatory markers in variant histologies of the bladder: is inflammation linked to survival after radical cystectomy?	PURPOSE: To investigate differences in standard preoperative inflammatory markers in patients with urothelial carcinoma (UC) and variant histologies undergoing radical cystectomy (RC) and determine its impact on survival. METHODS: Patients undergoing RC at an academic high-volume center were retrospectively analyzed. Preoperatively taken CRP, leukocytes, hemoglobin (Hb), and thrombocytes were analyzed as routine inflammatory biomarkers. Log-rank tests and Kruskal-Wallis analysis were used to calculate for differences in survival and in blood levels of biomarkers. RESULTS: 886 patients with complete follow-up and UC or variant histology underwent RC at our institution between 2004 and 2019. Although variant histology presents with significantly higher t stage than UC, cancer-specific survival (CSS) of UC (1-year-CSS: 93%) is not significantly different to variant histology of UC with squamous differentiation (UCSD, 1-year-CSS: 81%), squamous cell carcinoma (SCC, 1-year-CSS: 82%), and adenocarcinoma (AC, 1-year-CSS: 81%). In UC, alterations in all biomarkers except leukocytes beyond routine cut-off values were associated with poor survival (p < 0.01), whereas Hb beyond cut-off values are associated with poor prognosis in SCC (p < 0.05). CRP levels are significantly elevated in UCSD and SCC at time of surgery compared to UC (p < 0.05). CONCLUSION: Inflammatory biomarkers reveal distinctive patterns across UC and variant histologies of bladder cancer. As inflammation might play an important role in cancer progression, further research is warranted to understand those molecular mechanisms and their potential therapeutic impact in variant histology of bladder cancer.	bladder
Immunohistochemistry in hollow urinary tract.	There is no ideal marker or established immunohistochemistry panel to confirm urothelial differentiation. Immunohistochemistry must be always indicated in concrete differential diagnostic consideration. In this review article, immunohistochemistry will be discussed in the three different settings - distinction of benign and malignant changes of urothelium, the most frequent pitfalls and non-urothelial neoplasms of urinary tract.	bladder
PD-L1 expression in tumor-infiltrating lymphocytes (TILs) as an independent predictor of prognosis in patients with pN0 bladder cancer undergoing radical cystectomy.	OBJECTIVES: Checkpoint inhibitors have led to a paradigm shift in urothelial carcinoma (UC) treatment. However, the relationship between PD-L1 expression status and oncological outcomes in UC patients remains uncertain. Here, we investigated the prognostic value of PD-L1 expression status in patients with UC of the bladder (UCB) who underwent radical cystectomy (RC). MATERIALS AND METHODS: We retrospectively analyzed pathological specimens from 97 UCB patients treated with RC from 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining using SP263 was performed to evaluate PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). Kaplan-Meier plots and proportional Cox hazard ratios were examined to assess the relationship between PD-L1 expression and clinicopathological parameters and survival outcomes. RESULTS: Of the 97 specimens, 19.5% contained PD-L1-positive TCs, and 35.0% contained PD-L1-positive TILs. Regarding clinicopathological factors, PD-L1-positive TCs and TILs were significantly associated with high-grade tumors (TCs, P = 0.01; TILs, P = 0.003). Kaplan-Meier analyses showed that PD-L1-positive TCs were not correlated with survival rates. However, PD-L1-positive TILs were significantly associated with better recurrence-free survival (RFS; P = 0.03) and better cancer-specific survival (CSS; P = 0.02). Univariate analysis, but not multivariate analysis, CSS indicated that PD-L1-positive TILs were significant predictors of patient prognoses. Multivariate analysis showed that PD-L1-positive TILs independently predicted CSS in patients without lymph node metastasis (pN0). CONCLUSION: Positive PD-L1 expression is associated with high-grade tumors. PD-L1-positive TILs are independent predictors of favorable survival outcomes in surgically resected UCB patients at stage pN0.	bladder
A perioperative management to reduce rate of urinary tract infection for patient underwent radical cystectomy with ileal conduit diversion.	BACKGROUND: Although radical cystectomy, as the standard surgical treatment for muscle-invasive bladder cancer patients, prolongs survival remarkably, there are postoperative complications associated with urinary diversion. This study aimed to explore the antibiotic prophylaxis, according to culture of single J stent and urine from patients underwent urinary diversion (ileal conduit), its capacity to reduce the rate of urinary tract infection (UTI). METHODS: A total of 179 patients at Renji Hospital were reviewed in the study between Jan 2016 and June 2019. All patients included in this study were underwent radical cystectomy and ileal conduit. In Jan 2018, we enacted a quality initiative of urologic department to create a modified management. Following this initiative, antibiotic prophylaxis began to be used according to postoperative urine culture and stub of J-stent culture, which were obtained in 3rd days and 7th days after surgery, respectively. All consecutive patients treated with this process were compared with a conventional group. The clinicopathologic features of the two groups were compared using the t test and Chi square test. Multivariable logistic regression analysis was performed to determine the odds of developing 30-day UTI in two groups. RESULTS: 112 and 67 patients underwent the modified and conventional postoperative management, respectively. Two groups were comparable with regard to all demographic, clinical variables. The most common organism in urine culture and stub of J-stent culture was Candida albicans (38.46% and 31.7%). The rate of UTI was significantly lower in the modified group than in the conventional group (4.5% vs 13.4%, P = 0.031). In multivariable analyses, the conventional management was significantly more likely to develop UTI (OR = 4.992, 95% confidence interval [CI] 1.432-17.398 P = 0.012) than modified management. CONCLUSION: This procedure is associated with a significant decrease in UTI after surgery. During perioperative period, urine/single J stent culture with drug sensitivity test is necessary.	bladder
A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer.	Neoantigens arise from mutations in cancer cells and are important targets of T cell-mediated anti-tumor immunity. Here, we report the first open-label, phase Ib clinical trial of a personalized neoantigen-based vaccine, NEO-PV-01, in combination with PD-1 blockade in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. This analysis of 82 patients demonstrated that the regimen was safe, with no treatment-related serious adverse events observed. De novo neoantigen-specific CD4(+) and CD8(+) T cell responses were observed post-vaccination in all of the patients. The vaccine-induced T cells had a cytotoxic phenotype and were capable of trafficking to the tumor and mediating cell killing. In addition, epitope spread to neoantigens not included in the vaccine was detected post-vaccination. These data support the safety and immunogenicity of this regimen in patients with advanced solid tumors (Clinicaltrials.gov: NCT02897765).	bladder
COVID-19 infection threat in patients with high-risk non-muscle invasive bladder cancer receiving intravesical BCG therapy.	AIM: We evaluated the COVID-19 infection threat in patients receiving intravesical BCG therapy which has immunotherapeutic effects and is of vital importance in most of the individuals with high-risk non-muscle-invasive bladder cancer (NMIBC) and investigated the need for postponement of this therapy. METHODS: A total of 71 patients, who were diagnosed with high-risk NMIBC and on intravesical BCG treatment regularly (induction or maintenance), were enrolled in the study. The patients were classified into two groups depending on whether they were diagnosed with COVID-19 during the pandemic period or not. RESULTS: Of 71 patients, 26 underwent a COVID-19 polymerase chain reaction test with clinical suspicion during the pandemic period. Of these 26 patients, 4 were diagnosed with COVID-19. Age of the patients, working status (working/retired), compliance with containment measures against the pandemic, number of BCG courses, adverse effects after BCG therapy and systemic immune-inflammation index, which is an inflammation-related parameter, were not different between groups (P > .05). Neutrophil/lymphocyte ratio was significantly higher in the COVID-19 positive group (P < .05). COVID-19 positivity was higher in age groups 50-64 (6.6%) and 65-80 (5.8%) years than that in similar age groups of the normal population. CONCLUSION: Every effort should be made to administer intravesical BCG treatment in high-risk NMIBC patients even during the pandemic period. However, increased risk of COVID-19 transmission should be kept in mind and protective measures against COVID-19 for healthcare providers and patients before the procedure should be taken optimally. The procedure should be postponed in patients with lymphopenia in recent complete blood count.	bladder
Development and validation of a prognostic nomogram for predicting cancer-specific survival after radical cystectomy in patients with bladder cancer:A population-based study.	PURPOSE: To establish a prognostic model to estimate the cancer-specific survival (CSS) for urothelial carcinoma of bladder (UCB) patients after radical cystectomy (RC). METHODS: A total of 8650 candidates (2004-2011) obtained from the Surveillance, Epidemiology, and End Results (SEER) database were randomly split into development cohort (n = 4323) and validation cohort (n = 4327). We performed Cox regression analysis to identify prognostic factors and Kaplan-Meier analysis to assess survival outcome. A nomogram predicting CSS was constructed. Its performance was validated by calibration curves, the receiver operating characteristic (ROC) curves, concordance index (C-index), decision curve analysis (DCA), the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). RESULTS: The nomogram incorporated marital status, T stage, N stage, tumor size, and chemotherapy. In validation cohort, C-index of the nomogram was 0.707. AUC of the nomogram and AJCC stage were 0.767 versus 0.674. Calibration plots for 3- and 5-year CSS displayed good concordance. DCA curves of the nomogram exhibited larger benefits than the AJCC stage. The NRI and IDI indicated the nomogram outperformed AJCC stage. CONCLUSIONS: We have established a prognostic nomogram with improved discriminative ability and clinical benefits for UCB patients after RC. The nomogram alongside an easy access web tool may assist clinicians in optimizing the postoperative management.	bladder
Routine Preoperative Bone Scintigraphy Has Limited Impact on the Management of Patients with Invasive Bladder Cancer.	BACKGROUND: According to current guidelines, bone scintigraphy is not routinely indicated in patients with invasive bladder cancer prior to radical cystectomy unless specific symptoms are present. These guidelines, however, are based on sparse data of low quality. OBJECTIVE: To assess the clinical impact of routine staging bone scintigraphy on further patient management. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, single-center study of 1287 consecutive patients, who were scheduled to undergo radical cystectomy due to invasive bladder cancer between January 2000 and December 2017, was conducted. All patients were prospectively followed up according to our institutional protocol. INTERVENTION: Bone scintigraphy as staging imaging prior to radical cystectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the change in intended patient management. Secondary endpoints were the need for additional imaging, the diagnostic performance of baseline bone scintigraphy, and the association between clinical and radiological findings on bone metastases and survival. Logistic and Cox regression models were used for univariate and multivariate analyses. RESULTS AND LIMITATIONS: Of 1287 patients scheduled for radical cystectomy, 1148 (89%) underwent bone scintigraphy as staging imaging. Overall, baseline bone scintigraphy led to a change in the intended management in 19/1148 (1.7%) patients. Additional imaging was performed in 44/1148 (4%) patients. Although positive bone scintigraphy findings were associated with the occurrence/development of bone metastases, the diagnostic performance of baseline bone scintigraphy was generally poor (positive predictive value, negative predictive value, sensitivity, and specificity were 56%, 89%, 27%, and 96%, respectively). Higher clinical tumor stage and the nonperformance of cystectomy had negative impacts on cancer-specific survival and overall survival, while positive bone scintigraphy was associated with worse cancer-specific survival. This study was limited by its retrospective nature and the lack of follow-up bone scintigraphy in all patients. CONCLUSIONS: These results demonstrate the limited value of bone scintigraphy in the staging of invasive bladder cancer and do not support its routine use. PATIENT SUMMARY: In this study, we looked at the clinical impact of bone scintigraphy on the diagnostics of patients with invasive bladder cancer. We found that routine staging bone scintigraphy had limited impact on further patient management. We conclude that bone scintigraphy should not be part of routine staging in patients with invasive bladder cancer.	bladder
Spontaneous remission of untreated primary amyloidosis of the bladder after transurethral resection biopsy: a case report and literature review.	We herein present a case involving a 23-year-old woman with gross hematuria. Cystoscopy revealed abnormal areas of the mucosa along the anterior and posterior bladder walls. These abnormalities were suspicious for neoplasia; however, a diagnosis was not established by subsequent biopsy. The patient underwent transurethral resection biopsy in which an isolated lesion along the anterior wall was completely resected and the others were left untreated. Pathologic examination and special staining led to a diagnosis of amyloidosis, and the patient elected to undergo transurethral surgery 1 month later. During the operation, the intravesical lesions were found to have significantly improved in both the treated and untreated sites. The operation was cancelled, follow-up was arranged, and no other treatment was administered. Repeat cystoscopy examinations at 3 and 9 months after surgery showed that the lesions had almost completely disappeared.	bladder
SLC14A1 prevents oncometabolite accumulation and recruits HDAC1 to transrepress oncometabolite genes in urothelial carcinoma.	Urothelial carcinoma (UC), including upper tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC), is a common malignant disease in developed countries. Oncogenic metabolic lesions have been associated with UC development. Methods: Using data mining, a series of studies were performed to study the involvement of SLC14A1 in UC specimens, animal models and UC-derived cell lines. Results: In two cohorts of UTUC (n = 340) and UBUC (n = 295), the SLC14A1 protein level was an independent prognostic factor. Epigenetic silencing contributed to SLC14A1 downregulation in UCs. Total and membranous SLC14A1 played tumor suppressive roles through the inhibition of cell proliferation and metastasis in distinct UC-derived cells and animal models. Functional SLC14A1 prevented the accumulation of arginine and urea, enhanced mitochondrial fusion and aerobic respiration, inhibited glycolysis by altering the expression levels of several related proteins and sensitized arginine-deprivation treatment in ASS1-deficient UC-derived cells. In vitro and in vivo, SLC14A1 inhibited the mTOR signaling pathway and subsequently tumorigenesis, supported by reduced arginine concentrations in vitro. Nuclear SLC14A1 transrepressed HK2 and DEGS1 genes via recruitment of HDAC1 and/or SIN3A to maintain metabolic homeostasis and thereafter impeded tumorigenesis. Conclusion: Clinical associations, animal models and in vitro indications provide solid evidence that the SLC14A1 gene is a novel tumor suppressor in UCs. Total and membranous SLC14A1 prevents urea and arginine accumulation via the mTOR signaling pathway. Nuclear SLC14A1 recruits HDAC1 to transrepress oncometabolite genes.	bladder
Secondary adenocarcinoma of the urinary bladder attributed to metastatic gastroesophageal cancer.	Metastases of advanced gastrointestinal malignancy to the bladder is a rare phenomenon. Few such cases have been reported. Here, we describe the case of a man with recurrent local gastroesophageal adenocarcinoma who presented with acute kidney injury and bilateral ureteral obstruction ultimately found to have de novo metastatic esophageal disease in the urinary bladder.	bladder
Targetable gene fusions and aberrations in genitourinary oncology.	Gene fusions result from either structural chromosomal rearrangement or aberrations caused by splicing or transcriptional readthrough. The precise and distinctive presence of fusion genes in neoplastic tissues and their involvement in multiple pathways central to cancer development, growth and survival make them promising targets for personalized therapy. In genitourinary malignancies, rearrangements involving the E26 transformation-specific family of transcription factors have emerged as very frequent alterations in prostate cancer, especially the TMPRSS2-ERG fusion. In renal malignancies, Xp11 and t(6;11) translocations are hallmarks of a distinct pathological group of tumours described as microphthalmia-associated transcription factor family translocation-associated renal cell carcinomas. Novel druggable fusion events have been recognized in genitourinary malignancies, leading to the activation of several clinical trials. For instance, ALK-rearranged renal cell carcinomas have shown responses to alectinib and crizotinib. Erdafitinib has been tested for the treatment of FGFR-rearranged bladder cancer. Other anti-fibroblast growth factor receptor 3 (FGFR3) compounds are showing promising results in the treatment of bladder cancer, including infigratinib and pemigatinib, and all are currently in clinical trials.	bladder
Cell blocks in urine cytopathology: do they add value to the diagnosis? A pilot study.	INTRODUCTION: The utility of cell block (CB) preparation is well established in cytopathology. Despite 23.3% of College of American Pathologists-accredited laboratories using CB with liquid-based preparations on urine cytology (UC) cases, there are very few studies on their performance. To determine their usefulness, we conducted a retrospective review of UC cases that received CB. MATERIALS AND METHODS: We identified 27 UC cases with ThinPrep (TP) and CB preparation between 2016 and 2020 at our institution. Clinical history and follow-up data were compiled. A blinded review of TP alone, and TP together with CB, was performed by 2 pathologists and 2 cytotechnologists. Diagnoses were rendered in accordance with The Paris System for Reporting Urine Cytology. RESULTS: Blood and acute inflammation were common background elements in cases that received CB preparation. In total, CB upgraded the diagnosis in 7 of 27 cases (26%). The maximum utility of CB preparation was seen in indeterminate cases where 60% (6 of 10) were upgraded, including 71% (5 of 7) of atypical urothelial cells (AUC) and 30% (1 of 3) of suspicious for high-grade urothelial carcinoma (HGUC). One case (1 of 12, 8%) diagnosed as negative for HGUC on TP was diagnosed as low-grade urothelial neoplasia on CB. CONCLUSIONS: Our results demonstrate that adjunct use of CB preparation aids in a definitive diagnosis on AUC category and may be helpful in cases with cell clusters or tissue fragments, or cases suspicious for HGUC. Further correlation studies are warranted in this area to expand our knowledge about the utility of CBs in urine cytology.	bladder
Prognostic Role of Circular RNAs Expression in Bladder Carcinoma: A Meta-Analysis.	Background: Circular RNAs (circRNAs), a type of noncoding RNA, are associated with the occurrence and development of cancers. In recent years, their potential as biomarkers for bladder cancer (BC) has attracted increased attention. Aims: To reveal the value of circRNAs in the prognosis of BC. Methods: Relevant studies were collected to extract the clinicopathological data and overall survival (OS) of patients with BC. We then evaluated their tumor-related clinicopathological indicators using pooled odds ratio (OR) and 95% confidence interval (CI). Hazard ratio (HR) and 95% CI were used to estimate the OS of BC patients who expressed abnormal circRNAs. Results: The results indicate that seven circRNAs (circMYLK, circASXL1, hsa_circ_0000144, circ-VANGL1, circGprc5a, circZFR, and circ-cTFRC) whose expression was upregulated in tumor tissues, are associated with poor clinicopathological features (tumor/node/metastasis [TNM] stage: OR = 4.86, 95% CI: 2.53-9.34; histological grade: OR = 3.71, 95% CI: 2.37-5.79; lymph node metastasis: OR = 3.23; 95% CI: 2.15-4.88; recurrence: OR = 5.33; 95% CI: 2.27-12.52) and poor prognoses (OS: HR = 1.69; 95% CI: 1.17-2.44). We also found that seven circRNAs (circMTO1, circ-ITCH, circUBXN7, circFNDC3B, circ-ZKSCAN1, circPICALM, and circACVR2A) that were downregulated in tumors were associated with better clinicopathological indicators (TNM stage: OR = 0.23, 95% CI: 0.14-0.38; histological grade: OR = 0.21, 95% CI: 0.13-0.33; lymph node metastasis: OR = 0.26; 95% CI: 0.15-0.47) and better prognoses (OS: HR = 0.42; 95% CI: 0.30-0.58). Conclusion: Our results suggest that certain circRNAs are related to the clinicopathological characteristics and prognosis of BC patients, and may potentially be used as biomarkers.	bladder